OPTOVUE GETS FDA NOD FOR FIRST OCT ANGIOGRAPHY METRICS Optovue’s AngioAnalytics, which the company says is the world’s first optical coherence tomography angiography blood vessel measurement technology, received FDA 510(k) clearance... NEXY ROBOTIC RETINAL IMAGING SYSTEM FDA-CLEARED FOR U.S. MARKET Nexy, a new FDA 510(k)-cleared, CE-marked retinal camera, features fully robotic operation designed to yield clear and detailed retinal images, says its maker Next Sight (Prodenone, Italy)... And More...

Systemic Safety in Ranibizumab-treated Subjects with nAMD

This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg vs. sham ± verteporfin in individuals with neovascular age-related macular degeneration. In addition, researchers compared ranibizumab 0.3 mg and ranibizumab 0.5 mg to 0.3 mg with sham. To the researchers’ knowledge, this was the largest patient-level pooled analysis of individuals with nAMD treated with ranibizumab.

The researchers used patient-level pooled analysis of data from seven Genentech- and Novartis-sponsored Phase II, III and IV studies in nAMD completed by December 31, 2013. They performed pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) using Cox proportional hazard regression (hazard ratios, CIs) and rates per 100 patient-years.

Standardized Medical Dictionary for Regulatory Activities queries and extended searches helped researchers identify relevant safety endpoints, including arterial thromboembolic events, myocardial infarction, stroke or transient ischemic attack, stroke (excluding TIA), vascular deaths and major vascular events, as defined by the Antiplatelet Trialists’ Collaboration.

HRs for the primary comparison of ranibizumab 0.5 mg (n=480) vs. sham or verteporfin (n=462) were:
• 1.16 (CI, 0.72 to 1.88) for ATE;
• 1.33 (CI, 0.59 to 2.97) for MI;
• 1.43 (CI, 0.54 to 3.77) for stroke excluding TIA;
• 1.25 (CI, 0.61 to 2.55) for stroke or TIA;
• 0.57 (CI, 0.18 to 1.78) for vascular death; and
• 1.12 (CI, 0.64 to 1.98) for APTC events. HR CIs included one, indicating no significant treatment differences for all endpoints comparing ranibizumab 0.5 mg vs. sham or verteporfin.

Researchers determined that rates of cardiovascular and cerebrovascular events were low in individuals with nAMD and not clinically meaningfully different for those treated with ranibizumab 0.5 mg vs. sham or verteporfin. They wrote that these findings supported the favorable benefit-risk profile of ranibizumab in individuals with nAMD. Furthermore, they added, pooling studies enabled an analysis with higher power and precision compared with individual study analyses.

SOURCE: Zarbin MA, Francom S, Grzeschik S, et al. Systemic safety in ranibizumab-treated patients with neovascular age-related macular degeneration: A patient-level pooled analysis. Ophthalmology Retina 2018; June 11. [Epub ahead of print].

Combining En Face OCTA with Structural OCT & Blood Flow Analysis to Detect CNV in PEDs

Researchers described the morphology of pigment epithelial detachment using optical coherence tomography angiography and investigated its potential to detect choroidal neovascularization in various types of PEDs. The retrospective study included 53 individuals diagnosed with PED after undergoing OCTA (AngioPlex, Cirrus HD-OCT) and spectral-domain OCT (Spectralis SD-OCT).

Among 53 eyes:
• flat vascularized PED affected 21 eyes (40 percent);
• peaked vPED affected 10 eyes (19 percent);
• serous PED affected 12 eyes (23 percent);
• drusenoid PED affected six eyes (11 percent); and
• four eyes (7 percent) had multiple PED subtypes.

The main underlying etiologies were:
• pachychoroid spectrum disorder (30.2 percent);
• wet age-related macular degeneration (28.3 percent);
• central serous chorioretinopathy (18.9 percent);
• dry AMD (11.3 percent); and
• polypoidal choroidal vasculopathy (11.3 percent).

OCTA identified neovascularization in:
• 29 (94 percent) vPED eyes;
• two (17 percent) serous PED eyes; and
• four (100 percent) mixed PED eyes.

Researchers concluded that OCTA successfully identified neovascularization in vPEDs and PEDs previously considered to be non-neovascular. However, they recommended that clinicians combine structural OCT and blood flow analysis to accurately interpret PED-associated neovascularization.

SOURCE: Kang H, Byeon SH, Kim SS, et al. Combining en face optical coherence tomography angiography with structural optical coherence tomography and blood flow analysis for detecting choroidal neovascular complexes in pigment epithelial detachments. Retina 2018; May 8. [Epub ahead of print].

OCTA in Eyes with Indeterminate Choroidal Neovascularization

Investigators evaluated the use of optical coherence tomography angiography to detect choroidal neovascularization in eyes with indeterminate CNV features on conventional imaging, as part of a prospective, observational study of OCTA in individuals receiving routine spectral-domain optical coherence tomography for macular disease.

Participants included those enrolled in the Observational Assessment of Visualizing and Analyzing Vessels with Optical Coherence Tomography Angiography in Retinal (AVATAR) Diseases. In the AVATAR participants, CNV was considered part of a differential diagnosis based on clinical exams, prior imaging or both, but presence of CNV wasn’t definitive on SD-OCT and fluorescein angiography imaging. Participants had all undergone imaging with the Avanti RTVue XR HD (Optovue) and the Cirrus HD-OCT (Zeiss) systems. Several researchers are consultants for Zeiss.

Investigators assessed OCTA scans for the presence or absence of CNV. They evaluated spectral-domain OCT scans for the presence of fluid, hyperreflective material, serous pigment epithelial detachment, shallow irregular PED, vitreomacular adhesion, epiretinal membrane, retinal pigment epithelium atrophy and central subfield retinal thickness. They performed univariate and multivariate logistic regression analyses to identify features on SD-OCT associated with the presence of CNV on OCTA.

Twenty-nine eyes of 29 individuals met the criteria for inclusion. A CNV lesion was detected on OCTA in eight eyes (28 percent), while 21 eyes (72 percent) showed negative results for CNV. After adjusting for age, gender and central subfield retinal thickness, the presence on SD-OCT of shallow, irregular PED (OR, 148; CI, 3.22 to 6830; p=0.011) and combination intraretinal fluid and sub-RPE material (OR, 16.8; CI, 1.43 to 198; p=0.025) was associated significantly with the presence of CNV on OCTA.

Investigators found that OCTA enabled the identification of CNV that was otherwise indeterminate with prior imaging in select eyes. In addition, they determined that the presence of shallow, irregular PED as well as intraretinal fluid combined with sub-RPE material was associated with presence of CNV. Investigators suggested that OCTA might be a valuable adjunct to conventional SD-OCT and FA imaging in the detection and surveillance of CNV, particularly in diagnostic dilemmas.

SOURCE: Atsuro Uchida, MD, PhD, Deepa Manjunath, BA, Rishi P. Singh, et al. Optical coherence tomography angiography in eyes with indeterminate choroidal neovascularization. Results from the AVATAR Study. Ophthalmology Retina 2018; June 1. [Epub ahead of print].

Atrophy in nAMD

Scientists studied the development and progression of macular retinal pigment epithelial atrophy in eyes with neovascular age-related macular degeneration, and correlated the findings with visual acuity measurements, as part of a cohort study.

Participants included Age-Related Eye Disease Study 2 participants with intermediate AMD enrolled in a randomized controlled clinical trial of oral supplements. Scientists conducted analyses in a subset of AREDS2 participants who were also enrolled in the fundus autofluorescence ancillary study.

They assessed color photographs and FAF images in eyes with choroidal neovascularization, along with presence of geographic atrophy prior to CNV and development of macular atrophy after incident CNV. In addition, they measured hypoautofluorescence representing atrophy for area and macular involvement. And they analyzed the rate of atrophy and VA change over time.

Incident CNV developed in 334 eyes (9.2 percent) evaluated in the AREDS2 FAF sub-study. Of them, 40 percent showed macular atrophy at incidence of CNV, with half of cases attributable to pre-existing GA. Atrophy developed in 14.7 percent of eyes over four years of follow-up. Mean area of atrophy was largest in eyes with pre-existing GA and CNV (5.17 mm²; p<0.001), and atrophy involved the center of the macula in more than 65 percent of eyes. Mean VA letter score at the annual visit in which CNV was documented was similar in the three atrophy groups: eyes with CNV and pre-existing GA, incident atrophy at the first visit with CNV and eyes with atrophy during follow up (60 letters). Rate of atrophy also was similar in the three groups (range: 1.23 to 1.86 mm²; p=0.47). Eyes with macular atrophy lost more VA compared with eyes without atrophy, particularly after two years of follow-up (-10.9 vs. -3.6 letters; p=0.07).

Scientists concluded that presence of atrophy was common in neovascular AMD and often could be attributed to pre-existing GA. They added that macular atrophy and GA appeared to be a continuum of the same disease process, with both associated with poor vision.

SOURCE: Domalpally A, Danis RP, Trane R, et al. Atrophy in neovascular age-related macular degeneration. Age-Related Eye Disease Study 2 Report Number 15. Ophthalmology Retina 2018; June 2. [Epub ahead of print].

Using OCTA to Assess Neovascularization Characteristics in Early PDR

Researchers classified retinal neovascularization in untreated early stages of proliferative diabetic retinopathy based on optical coherence tomography angiography, as part of a cross-sectional study. Thirty-five eyes were included. They underwent color fundus photography, fluorescein angiography and OCTA exams. Researchers used OCTA to assess neovascularization of the optic disc, neovascularization elsewhere and intraretinal microvascular abnormalities. They evaluated the origin and morphology of NVD/NVE/IRMA on OCTA, and measured retinal nonperfusion areas using Image J software.

Researchers captured 35 NVDs, 75 NVEs and 12 IRMAs in 35 eyes, and identified three proposed subtypes of NVEs based on origins and morphological features.
• Type 1 (32 of 75, 42.67 percent) originated from retinal vein structures in a tree-like shape; type 2 (30 of 75, 40 percent) originated from capillary networks, with an octopus-like appearance; and type 3 (13 of 75, 17.33 percent) originated from the IRMAs, having a sea fan shape.
• NVDs originated from the retinal artery, retinal vein or choroid, and arose from the bending vessels near the rim of the optic disc.
• IRMAs originated from, and drained into, retinal venules extending into the retina.

The initial layer and affiliated NPAs were significantly different in the three subtypes of NVEs (all p<0.01).

Researchers wrote that OCTA enabled identification of the origins and morphological patterns of neovascularization in PDR. They added that the new classification of retinal neovascularization might be useful to better understand pathophysiological mechanisms and guide efficient therapeutic strategies.

SOURCE: Pan J, Chen D, Yang X, et al. Characteristics of neovascularization in early stages of proliferative diabetic retinopathy by optical coherence tomography angiography. Am J Ophthalmol 2018; May 26. [Epub ahead of print].

Retinal Vessel Geometric Characteristics and DR Incidence & Progression

Scientists examined the relationships between retinal vessel geometry and the incidence and progression of diabetic retinopathy, as part of an observational, prospective cohort study.

A total of 996 individuals with type 1 diabetes mellitus, and 1,370 people with type 2 diabetes mellitus at a baseline exam were eligible for follow-up exams at five-year intervals. A total of 3,846 person-interval data from these follow-ups were the basis for the analyses.

Scientists graded 30-degree stereoscopic color fundus photographs to assess DR and macular edema. They analyzed retinal vessel geometric characteristics using the Singapore I Vessel Assessment program from a digitized copy of one field 1 fundus photograph obtained at baseline and follow-up.

Main outcome measures included the five-year incidence of DR, progression of DR, incidence of proliferative DR and clinically significant macular edema in right eyes.

• Incident DR occurred in 45 percent of eyes, progression occurred in 32 percent, PDR was found in 10 percent and CSME was detected in 5 percent of eyes.
• While adjusting for glycated hemoglobin, duration of diabetes and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of DR (OR, 1.17; CI, 1.01 to 1.35).
• Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; CI, 1.03 to 1.36).
• Retinal venular curvature tortuosity was associated significantly with incidence of PDR (OR, 1.15; CI, 1.01 to 1.30).
• Retinal venular branching angle (OR, 1.41; CI, 1.10 to 1.82) was associated significantly with the incidence of CSME.
• No significant associations of other RVGCs with DR outcomes in the full multivariate model were found.
• Inclusion of all possible RVGCs didn’t improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level.

Scientists found that geometric characteristics of retinal venules were associated with progression of DR. However, they also determined that most RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in type 1 diabetes mellitus and type 2 diabetes mellitus.

Source: Klein R, Lee KE, Danforth L, et al. The relationship of retinal vessel geometric characteristics to the incidence and progression of diabetic retinopathy. Ophthalmology 2018; May 17. [Epub ahead of print].

Subjective VA Evaluation for Detecting Disease Activity in Exudative Maculopathies

Individuals with exudative maculopathies (neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion) are faced with burdensome exams and treatments. As such, researchers aimed to analyze the accuracy of subjective evaluations of visual acuity and metamorphopsia to detect disease reactivation compared with spectral-domain optical coherence tomography to assess morphological signs of reactivation.

Researchers conducted a retrospective study of 888 individuals treated for nAMD (n=638): DME (84); BRVO (110); and CRVO (56). They compared subjective evaluations (i.e., change of VA and/or metamorphopsia) against clinical evaluations via SD-OCT of disease activity. And they calculated sensitivity and specificity, and negative and positive predictive values for detection of active disease. They also analyzed via regression analyses false-negative subjective evaluations.

The sensitivity of subjective evaluations to detect disease reactivation was <0.50 in all exudative maculopathies. Sensitivity was increased to ≥0.60 by combining subjective worsening with one lost line in the VA test in RVO, but not in DME and nAMD. The specificity was >0.85 in all individuals, and the positive predictive value was >0.85 in people with RVO. Regression analyses didn’t reveal any factors that could reliably identify subgroups in which OCT could be omitted, although CRVO subjects with a VA of <0.3 logMAR had an odds ratio of 0.20 for false-negative subjective evaluations (p=0.009).

Researchers found the accuracy of subjective evaluations to discriminate disease activity in individuals with different exudative maculopathies was low and didn’t substitute for frequent SD-OCT exams. They added that routinely assessed clinical parameters such as age, VA or treatment experience weren’t useful to predict the validity of subjective evaluation of disease activity.

SOURCE: Bruender M-C, Benjamin N, Hansjuergen TA, et al. Subjective evaluation of visual acuity is not reliable to detect disease activity in different exudative maculopathies. Graefes Arch Clin Exp Ophthalmol 2018; June 1. [Epub ahead of print].

Rates of Endophthalmitis After PPV

Researchers studied the incidence of endophthalmitis after pars plana vitrectomy, its causative organisms and visual acuity outcomes in a retrospective, comparative study.

They reviewed the medical records of individuals with acute-onset postoperative endophthalmitis after PPV at Farabi Eye Hospital, Tehran, Iran, during a 12-year period between January 2004 and November 2015. They developed a control group by gathering the data from surgical records to compare the endophthalmitis cases with other cases that underwent PPV on the same day in the same operating room.

The incidence rate of post-vitrectomy endophthalmitis was 0.04 percent (16/39,783). The organisms identified in aqueous or vitreous cultures (culture positive: 44 percent) included Streptococcus pneumoniae (two individuals, 12.5 percent), Pseudomonas aeruginosa (two individuals, 12.5 percent), fungi (two individuals, 12.5 percent), and Streptococcus viridans (one individual, 6.25 percent). Visual acuity after treatment for endophthalmitis ranged from light perception (seven eyes) to hand motion (one eye), and evisceration was performed in eight eyes (50 percent). When comparing cases (individuals developing endophthalmitis) and controls (subjects with no complications operated on the same day and at the same place as the case group), not using tamponade showed a statistically significant relationship with the occurrence of endophthalmitis (p=0.034).

Researchers determined a low incidence of endophthalmitis after PPV comparable with previous studies that had resulted in poor visual acuity. They speculated that the lack of a tamponade might have increased the risk of endophthalmitis among subjects.

SOURCE: Tabatabaei SA, Soleimani M, Vakili H, et al. The rate of endophthalmitis after pars plana vitrectomy and its risk factors. Int Ophthalmol 2018; May 11. [Epub ahead of print].